Developmental Toxicology Studies of Fluoxetine Hydrochloride Administered Orally to Rats and Rabbits

Pregnant Fischer 344 rats were given fluoxetine orally at dose levels of 0, 2, 5, or 12.5 mg/kg on Gestation Days (GD) 6–15; pregnant Dutch Belted rabbits were given 0, 2.5, 7.5, or 15 mg/kg orally on GD 6–18. Cesarean sections were performed on rats and rabbits on GD 20 and 28, respectively. In rats, maternal toxicity was indicated at 12.5 mg/kg by depression of weight gain and food consumption. Fetal viability, weight, and morphology were not affected at any dose level. Maternal and developmental No Observed Adverse Effect Levels (NOAELs) in the rat were 5 and 12.5 mg/kg, respectively. In rabbits, weight loss occurred at 2.5,7.5, and 15 mg/kg. Food consumption was also depressed at 7.5 and 15 mg/kg; abortions and maternal mortality occurred secondarily to anorexia and cachexia at 15 mg/kg. Fetal viability, weight, and morphology were not affected at any dose level. A NOAEL for maternal effects was not established in the rabbit; the NOAEL for developmental effects in the rabbit was 15 mg/kg. Based on these data, fluoxetine did not exhibit any toxicity toward the developing rat or rabbit conceptus at doses that were maternally toxic.